Evaluating solubility, stability, and inclusion complexation of oxyresveratrol with various β-cyclodextrin derivatives using advanced computational techniques and experimental validation
Issued Date
2024-10-01
Resource Type
ISSN
14769271
Scopus ID
2-s2.0-85196003208
Journal Title
Computational Biology and Chemistry
Volume
112
Rights Holder(s)
SCOPUS
Bibliographic Citation
Computational Biology and Chemistry Vol.112 (2024)
Suggested Citation
Ali S., Aman A., Hengphasatporn K., Oopkaew L., Todee B., Fujiki R., Harada R., Shigeta Y., Krusong K., Choowongkomon K., Chavasiri W., Wolschann P., Mahalapbutr P., Rungrotmongkol T. Evaluating solubility, stability, and inclusion complexation of oxyresveratrol with various β-cyclodextrin derivatives using advanced computational techniques and experimental validation. Computational Biology and Chemistry Vol.112 (2024). doi:10.1016/j.compbiolchem.2024.108111 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/98898
Title
Evaluating solubility, stability, and inclusion complexation of oxyresveratrol with various β-cyclodextrin derivatives using advanced computational techniques and experimental validation
Corresponding Author(s)
Other Contributor(s)
Abstract
Oxyresveratrol (OXY), a natural stilbenoid in mulberry fruits, is known for its diverse pharmacological properties. However, its clinical use is hindered by low water solubility and limited bioavailability. In the present study, the inclusion complexes of OXY with β-cyclodextrin (βCD) and its three analogs, dimethyl-β-cyclodextrin (DMβCD), hydroxypropyl-β-cyclodextrin (HPβCD) and sulfobutylether-β-cyclodextrin (SBEβCD), were investigated using in silico and in vitro studies. Molecular docking revealed two binding orientations of OXY, namely, 4′,6′-dihydroxyphenyl (A-form) and 5,7-benzenediol ring (B-form). Molecular Dynamics simulations suggested the formation of inclusion complexes with βCDs through two distinct orientations, with OXY/SBEβCD exhibiting maximum atom contacts and the lowest solvent-exposed area in the hydrophobic cavity. These results corresponded well with the highest binding affinity observed in OXY/SBEβCD when assessed using the MM/GBSA method. Beyond traditional simulation methods, Ligand-binding Parallel Cascade Selection Molecular Dynamics method was employed to investigate how the drug enters and accommodates within the hydrophobic cavity. The in silico results aligned with stability constants: SBEβCD (2060 M−1), HPβCD (1860 M−1), DMβCD (1700 M−1), and βCD (1420 M−1). All complexes exhibited a 1:1 binding mode (AL type), with SBEβCD enhancing OXY solubility (25-fold). SEM micrographs, DSC thermograms, FT-IR and 1H NMR spectra confirm the inclusion complex formation, revealing novel surface morphologies, distinctive thermal behaviors, and new peaks. Notably, the inhibitory impact on the proliferation of breast cancer cell lines, MCF-7, exhibited by inclusion complexes particularly OXY/DMβCD, OXY/HPβCD, and OXY/SBEβCD were markedly superior compared to that of OXY alone.